Antibiotic therapy (CH13) Flashcards
what are antibiotics selectively toxic to?
selectively toxic to bacteria without toxicity to eukaryotic organisms
- “magic bullet” concept
- still have unintended SEs: age, cell, metabolism dependent, allergies
Bactericidal vs Bacteriostatic
bactericidal = kills pathogens
bacteriostatic = prevents bacterial growth –> immune response able to get rid of pathogen
Narrow or broad spectrum? Ampicillin, penicillin, isoniazid
ampicillin –> gram (+) & gram (-) = broad spectrum
penicillin –> gram (+) = narrow spectrum
isoniazid –> very narrow spectrum
How do we measure effectiveness of abx?
- in vitro tests for abx effectiveness
- minimal inhibitory concentration (MIC) (determines potency + susceptibility to abx)
- minimal bactericidal concentration (MBC) (lowest conc need to kill bac) –> reqs further plating to determine if any cells survived
What are the disk diffusion assays?
- kirby-bauer assay - determines how susceptible bacteria are to abx
- zone of inhibition - measured around filter-paper disks impregnated with 12 abxs
Clinical Considerations for Usefulness of Abx
- drug’s concentration in tissue (based on its half-life) > MIC at all times during treatment
- higher doses than MIC or multiple doses to keep the levels greater than lab MIC
Chemotherapeutic index
ratio of toxic dose to therapeutic dose
- the higher the chemotherapeutic index, the safer the drug
therapeutic dose vs toxic dose
therapeutic dose = minimum dose/kg of body weight that stops growth
toxic dose = max dose tolerated by the pt
Synergism & antagonism with abx
- combos of abx can be syngergistic or antagonistic
- synergistic drugs have greater effectiveness when used tgt, e.g., aminoglycoside & vancomycin
- antagonistic drugs interfere with e/o & decr effectiveness (e.g., penicillin + macrolides)
What is directed therapy?
directed antimicrobial regimens prescribed to target a specific pathogen(s), usually informed by the results of mcirobiological investigations
What is empirical therapy?
- antimicrobial regimen used when a clinical diagnosis of an infection has been made, and a delay in initiating therapy (to wait for microbiological results) would be inappropriate
What are the 3 ways of classifying antibacterial agents?
- bactericidal or bacteriostatic
- target site (5)
- chemical structure
Where do antibiotics work?
- metabolic inhibitors (intermediary metabolism)
- protein synthesis inhibitors (30s + 50s)
- RNA replication inhibitors
- RNA polymerase inhibitors (transcription)
- cell wall inhibitors
- cell membrane damage
- mycolic acid synthesis
what are the metabolic inhibitors?
- sulfonamide + trimethoprim (inhibit folic acid synthesis
- metronidazole
- bedaquiline (inhibits ATP synthase in m. tuberculosis)
- platensimycin (inhbits bacterial fatty acid synthesis)
what are the cell wall inhibitors?
- penicillins
- cephalosporins
- vancomycin
- bacitracni
- monobactams
which abx target cell membrane integrity?
- polymyxins
- gramicidin (antibacterial)
- amphotericin
- imidazoles (antifungal)
which abx target mycolic acid synthesis?
- isoniazid (Mycobacterium tuberculosis)
What abx target DNA replication and integrity?
- quinolones
- metronidazole
- nitrofurantoin
- some antiviral compounds
what abx targets transcription/RNA polyemerase inhibitors?
- rifampin
- fidaxomicin (c. diff)
Which abx targets protein synthesis?
50s:
- chloramphenicol
- macrolides (erythromycin)
- clindamycin
- oxazolidones (linezolid)
- streptogramins (quinupristin-dalfopristin)
- lincosamides
30s:
- aminoglycosides (gentamicins)
- tetraclyclines (doxyclycline)
What do abx that target cell walls usually kill?
abx targeting cell wall biosynthesis generally kill only growing cells
what are beta-lactam antibiotics? which abx are apart of this?
- have specific chemical structure called beta-lactam ring
- penicillin and related abx bind to Penicillin-Binding Proteins (PBPs) that bacteria use to build cell walls
What are penicillin-binding proteins?
enzymes that produce cross-links in peptidoglycan
Antibiotic resistance for beta-lactam abx
- HGT or mutation followed by natural selection
- bacteria resistance to cell wall-inhibiting antibiotics
- beta-lactamase produced by bacteria
- beta-lactam ring broken –> abx no longer effective
